IAI Accepts, published online ahead of print on 19 October 2009

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Infect. Immun. doi:10.1128/IAI.00864-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Interactions of human monocyte-derived dendritic cells and Klebsiella pneumoniae : the roles of capsule and LPS O-antigen unravelled.

B. Evrard^*, D. Balestrino, A. Dosgilbert, J-L J. Bouya-Gachancard, N. Charbonnel, C. Forestier, and A. Tridon

CHU Clermont-Ferrand, Laboratoire d'Immunologie, Clermont-Ferrand, France; Université d'Auvergne-Clermont1, UFR Médecine-Pharmacie, Laboratoire d'Immunologie, Clermont-Ferrand, France; Université d'Auvergne-Clermont1, UFR Pharmacie, Laboratoire de Bactériologie, Clermont-Ferrand, France

^* To whom correspondence should be addressed. Email: bevrard{at}chu-clermontferrand.fr.

In humans, Klebsiella pneumoniae is a saprophyte bacterium of the nasopharyngeal and intestinal mucosae that is also frequently responsible for severe nosocomial infections. Two major factors of virulence, capsular polysaccharide (CPS) and lipopolysaccharide (LPS) O-antigen, are involved in mucosal colonization and the development of infections. These bacterial surface structures are likely to play major roles in the interactions with the mucosal immune system, which is orchestrated by a network of surveillance based on dendritic cells (DCs). To determine the role of K. pneumoniae CPS and LPS in DC response, we investigated the response of human monocyte-derived immature DCs to bacterial challenge with a wild-type strain and its isogenic mutants deficient in CPS or LPS O-antigen production. As observed by flow cytometry and confocal laser microscopy, the rate of phagocytosis was inversely proportional to the amount of CPS on the bacterial cell surface, with LPS playing little or no role. K. pneumoniae wild-type strain induced DC maturation with upregulation of CD83, CD86, TLR4 and downregulation of CD14 and DC-SIGN. With CPS mutants, we observed a greater decrease in DC-SIGN, suggesting a superior maturation of DCs. In addition, incubation of DCs with CPS mutants, and to a lesser extent with LPS mutants, resulted in significantly higher Th1 cytokine production. Combined, our findings suggest that K. pneumoniae CPS, by hampering bacterial binding and internalization, induces a defective immunological host response, including maturation of DCs and pro-Th1 cytokine production whereas the LPS O-antigen seems to be involved essentially in DC activation.